1. Field of the Invention
The present invention relates to a peptide that permeates the blood-brain barrier, a drug transporter, an antipoliovirus agent, a blood-brain barrier permeating agent, and a transferrin receptor capturing body.
2. Description of the Related Art
The blood-brain barrier (BBB) in the central nervous system strictly restricts intake of substances to the central nervous system. This is because the blood-brain barrier is physically narrowed with densely populated vascular endothelial cells and other cells, and these cells have physiological functions of restricting intake of substances. The mechanism of permeation of substances through the blood-brain barrier has not yet been revealed. At present, even if disorders occur in the central nervous system, drugs cannot be delivered to target sites in the central nervous system.
Disorders in the central nervous system include: infections caused by, for example, poliovirus and Japanese encephalitis virus; and neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's chorea. Infections in the central nervous system have been prevented by vaccination, and infected patients have mainly undergone symptomatic therapy. In this manner, effective therapeutic methods have not yet been found.
One proposed therapeutic drug against poliovirus is an antivirus agent composition containing citric acid and/or zinc, L-arginine and an acceptable carrier (see Japanese Patent Application Laid-Open (JP-A) No. 2009-298800) and another proposed therapeutic drug is an antivirus agent containing selegiline as an active ingredient (see JP-A No. 2004-292399). These antivirus agents cannot permeate the blood-brain barrier, which is problematic in use.
In an attempt to utilize drugs more safely and effectively, the recent interest has focused not only on the dosage form suitable to drugs but also on drug delivery methods for efficiently delivering drugs to target sites in the body. In particular, demand has arisen for practical use of a drug delivery system (DDS) as a transporting system for delivering a drug at a required timing in a required amount to a required site.
In the central nervous system, a method using a virus vector has been proposed (see, for example, JP-A No. 2009-159988). However, this method has a problem in terms of safety and has not been practically used so far. At present, there has not been found a DDS that allows drugs to permeate the blood-brain barrier.
Meanwhile, viruses permeate the blood-brain barrier to infect the central nervous system. For example, poliovirus (PV), which is a positive single-stranded RNA virus belonging to the genus Enterovirus of the family Picornaviridae, is a cause of polio (poliomyelitis) and known to have neurotropism. A natural host thereof is only human but experimentally, poliovirus can infect primates. Poliovirus infects human via an oral route, proliferates in the digestive tract, and invades blood via the tonsil or the Peyer's patch. Then, poliovirus permeates the blood-brain barrier to invade the central nervous system, where it mainly infects motor nerve cells to destroy their cell functions. As a result, infected patients suffer from paralysis of their limbs. The central nervous system is also known to have a route through which poliovirus is transported from the skeletal muscle in a retrograde fashion on the nerve axon to reach motor nerve cells.
As for a poliovirus receptor (PVR), CD155 is known to be involved with poliovirus infection (see Koike S et al., EMBO J. 1990 October; 9(10): 3217-24.).
However, studies using a transgenic mouse with a PVR gene introduced suggest that CD155 is not involved with the permeation of poliovirus through the blood-brain barrier (see Yang W X et al., Virology. 1997 Mar. 17; 229(2): 421-8.). This finding indicates that another receptor is presumably involved with the permeation of poliovirus through the blood-brain barrier.
Although revealing the mechanism of poliovirus infection is thought to reveal the blood-brain barrier permeation mechanism from blood to the central nervous system, the mechanism of poliovirus infection has not yet been revealed.